Device for dosage of substances

ABSTRACT

A device for dosage of substances having a substance intake portion, which included at least one substance compartment for the intake of substance to be dosed, an emptying portion for the emptying the substance compartment and a weighing balance for the determination of the quantity of dosed substance, wherein the substance intake portion includes a plurality of substance compartments, which are able to be individually emptied. The device further includes a control means, which control the emptying of the substance compartments in a manner dependent on the quantity of dosed substance, which is determined by means of the weighing balance.

FIELD OF THE INVENTION

The present invention relates to a device and a method for dosage ofsubstances.

BACKGROUND

In many cases in the laboratory the dosage of substances takes place incontainers by manual addition with a spatula into the container to befilled, or into an intermediate container, which is subsequently emptiedinto the container to be filled, wherein the container or intermediatecontainer is placed on a weighing balance. The achievable precision islimited thereby by the ability of the experimenter. These actions canonly be automated with great technical effort. In addition theoverdosages which frequently occur are only laboriously manuallycorrected and when automated, with still greater effort. Moreover, notevery container can be placed on a weighing balance, and even if this ispossible, one can not dose independent of the location.

For these reasons a dosing device, disclosed in WO 02/29369 A1, wasdeveloped by the firm Chemspeed Ltd., CH-4302 Augst, which enables acontinuous dosage, which is gravimetrically controlled from above, intoany container in any location within the operating capacity of a roboticarm. However in this case the dosing device has to be adjusted to thesubstance to be dosed and/or the substance has to fulfill certainrequirements concerning flowability or the flow behaviour, in order tobe able to be continuously dosed.

SUMMARY

In view of the disadvantages of the previously known devices and methodsdescribed above, the invention is based on the following object: toprovide a device and a method for dosage of substances of the typementioned at the outset, which for substances which vary in regards toconsistency, reactivity, morphology etc., enable an exact, simple andautomatable dosing of a desired quantity of substance.

This object is achieved through the device according to the inventionand the method according to the invention. Preferred embodiments arefound in the dependent claims.

The essence of the invention consists of the following: a device fordosage of substances has a substance intake portion, which comprises aplurality of substance compartments for the intake of substance to bedosed, which are individually emptiable. The device comprises inaddition an emptying portion for the emptying of the substancecompartments, a weighing balance for the determination of the quantityof dosed substance and control means which control the emptying of thesubstance compartments in a manner dependent on the quantity of dosedsubstance, which is determined by means of the weighing balance.

Since the substance intake portion has a plurality of substancecompartments, which are individually emptiable, and that a weighingbalance is used for the determination of the quantity of dosedsubstance, diverse substances can be progressively precisely dosed withhigh speed by means of an approximation technique. The substances are,for example, in fluid, powdery or solid form or they can also be anarbitrary mixture of solid or fluid substances and be of diverseconsistencies. The approximation technique can be automated withoutproblem. In addition, dosage can very simply take place from many supplycontainers into many target vessels. In addition, at least then thedosage is not bound to a location, if a weighing balance is used, whichmeasures from above the weight of the substance intake portion, theemptying portion and the substance present in the substancecompartments.

The control means comprises for example a calculator unit with aprocessor and electrical circuits for the weighing balance and for theemptying portion.

In the case of an advantageous embodiment, the substance intake portioncomprises substance compartments of various size classes, with whichvarious quantities of substance to be dosed can be intaken. This enablesa rapider approximation of the desired dosage quantity, since firstly arough approximation can be carried out with larger substancecompartments, which can then be refined by the emptying of smallersubstance compartments. Additionally a large range can be covered by thevarious size classes and yet still be dosed with high resolution.

Preferably at least some of the size classes are graduated across atleast a factor of 5, for example in the ratio 1:2:5. With anadvantageous alternative the size classes are graduated across a factorof 9, for example in the ratio 1:3:9. Since a processor normallyundertakes the computations necessary for the dosage, optionally alsonon-integer ratios are usable, which can for example result from theproduction of the substance compartments.

With an advantageous embodiment at least some of the substancecompartments are pre-filled with substance to be dosed and preferablyare sealed. The substance compartments can for example be purchasedpre-filled and/or stored pre-filled and then if required be received bythe device according to the invention and be emptied. The seal can forexample consist of a foil, which is peeled off as a whole directlybefore use or, alternatively to that, opened by a pressure surge usedfor the emptying of the substance compartment or another physical orchemical process, in such a way that it advantageously rips so that noremains of the foil fall in the vessels to be filled. E.g. it is alsopossible on a carrier plate to first fill up various substancecompartments with various substances, wherein these can have variousphysical and chemical properties.

With advantage the substance compartments are formed by verticallyarranged tubes. These tubes are for example cylindrical and made fromglass, plastic or metal. To take in substance they are preferably dippedin or inserted in the substance and then taken out again. This can besimply automated, it needs only a piece of equipment for verticaldisplacement of the substance compartments or of the supply containercontaining the substance.

Preferably the tubes of different size classes have different innerdiameters. In the case of dipping or inserting the tubes in thesubstance and subsequent removal of the tubes, with sufficiently smallinner diameters, different substance quantities then adhere in the tubesof different size classes.

Advantageously the inner diameters of the tubes are smaller than 5 mm,preferably smaller than 1 mm, more preferably smaller than 0.5 mm, inparticular preferably smaller than 0.1 mm. Thus it is guaranteed thatalso very fine powdery substances, as well as fluid substances, can beintaken by the tubes.

Preferably at least some of the tubes narrow from the top to the bottom.Thus more space is available on the top for the emptying portion or thetaking in of substance.

In the case of an advantageous embodiment, at least some of the tubeshave pointed or sharp-edged lower sections. This enables a simplerinsertion in powdery or solid substances and with fluid substances leadsto a more regular release of drops, i.e. to a more uniform fill level oftubes of the same size class.

In the case of an advantageous embodiment, at least some of the tubesare pre-filled with substance to be dosed, wherein preferably the twoends of the tubes are sealed with a foil. The tubes can for example bepurchased pre-filled and/or be stored pre-filled and then if required bereceived by the device according to the invention and be emptied.

With advantage at least some of the substance compartments have an innersurface with an arithmetic mean roughness value R_(a) larger than 0.5μm. Thus the intaken substance is held well.

In the case of an advantageous embodiment the device according to theinvention comprises various classes of substance compartments with innersurfaces with different arithmetic mean roughness values R_(a). Sincethe inner surfaces of the substance compartments of different classeshave different arithmetic mean roughness values R_(a), the classes ofsubstance compartments concerned retain different quantities ofsubstance. This enables a rapider approximation of the desired dosagequantity.

Preferably at least some of the substance compartments have on theirinner surface flexible lamellae and/or barbs. Thereby the substance tobe dosed is better retained in the substance compartment.

In the case of an advantageous embodiment, the device according to theinvention comprises various classes of substance compartments with innersurfaces with different wettability. Thereby capillary forces can beoptimally capitalized on and the concerned substance compartments ofdifferent classes can retain different quantities of fluid substance,which enables a rapider approximation of the desired dosage quantity.

With advantage the substance intake portion is automatically removablefrom the emptying portion, for example through pulling off at a fixedpart. Substance intake portions can thus be automatically exchanged, forexample with a change of substance and if need be are also designed costeffectively for one time usage, whereby the danger of impurities fromother substances to be dosed can be ruled out.

Preferably the substance compartments are individually mounted in thesubstance intake portion and their number is variable. Thus as manysubstance compartments in a class can be mounted as precisely needed.

Preferably the substance compartments in the substance intake portionare individually displaceably mounted between a fill position, in whichthey are fillable, and an inactive position, in which they are notfillable. Therefore, as many substance compartments of a class can bebrought into the fill position as precisely needed. The displaceabilityof the substance compartments can for example be guaranteed by theirposition in pipes, from which they can be moved out.

Advantageously the device according to the invention comprises means forvertical displacement of the substance intake portion. This enables thedipping in or insertion of the substance compartments in a simple way inthe substance to be intaken and the further taking out of the substancecompartments.

In the case of a preferred embodiment the emptying portion comprisesmeans for the admission of pressure gas into every individual substancecompartment. A pneumatic or another pressure surge can be produced forexample by opening a valve, irreversible destruction of a componentprovided therefor or by emptying a pressure container. By the admissionof pressure gas, a substance compartment can be emptied in a simplemanner.

In the case of an alternative advantageous embodiment, for everysubstance compartment the emptying portion has a displaceable piston.With this piston the substance can then be expelled out of the substancecompartment. Another mechanical component can also be used instead of apiston. The displacement of the piston or other mechanical component canbe brought about for example by motors, springs, magnets or piezoelements.

In the case of another alternative embodiment the emptying portion hasmeans for the alteration of the geometry of every individual substancecompartment, which preferably comprise means for the production of amechanical pressure, a voltage or a temperature change. The means forproduction of a mechanical pressure comprise for example piezo elements,in particular piezo ceramic composite elements. Through the change ofgeometry, the intaken substance can be released from the substancecompartment and this can thus be emptied.

In the case of yet another alternative embodiment, the emptying portionhas means for the alteration of the surface properties of the innersurface of every individual substance compartment, which preferablycomprise means for the production of a voltage and/or a temperaturechange. By the alteration of the surface properties, the intakensubstance can be released from the substance compartment and this canthus be emptied.

In the case of a further alternative embodiment, the emptying portionhas means for the alteration of the flow properties of the substance tobe dosed in every individual substance compartment, which preferablycomprise means for the production a voltage or a temperature change. Bythe alteration of the flow properties of the substance to be dosed, theintaken substance can be released from the substance compartment andthis can thus be emptied.

Advantageously the emptying portion and the substance intake portion arearranged on the weighing balance, such that they are weighed by thisweighing balance. The arrangement of the emptying portion and thesubstance intake portion takes place for example as described in WO02/29369 A1 for a customary dosing device. By this weighing from above,the amount of substance that is dispensed by the emptying of a substancecompartment can be determined. The device according to the invention isso much more independent of location than in the case of the presence ofa weighing balance beneath the vessel to be filled with substance. Forexample dosing can occur in the entire operating range of a robotic arm.

Alternatively to weighing from above, also only the dosing device can bearranged above the vessel to be filled, if this stands on a weighingbalance.

It is also possible to work with two weighing balances: on one thedosing system is attached, a second stands under the vessel to befilled, for the control of the upper weighing balance.

Alternatively, the weighing balance, or a second weighing balance, isdesigned in order to receive a vessel to be filled and to measure theweight of the vessel and the substance dosed into the vessel. Anadvantage of this alternative is the fact that the weight of the alreadydosed substance, and not only the weight of the expelled substance ismeasured, which rules out a source of error. In case two weighingbalances are used, advantageously at least one equally precise is usedunderneath. The second weighing balance can thereby directly measure thetarget vessel to be filled or an intermediate container, in which thesubstance is pre-dosed.

The method according to the invention for dosage of substances with adevice according to the invention consists essentially of:

-   -   a) by emptying at least one substance compartment of a substance        intake portion containing substance, substance is dosed into a        vessel;    -   b) the quantity of dosed substance is determined with a weighing        balance;    -   c) by control means it is calculated whether, and if need be,        how much substance is still to be dosed into the vessel, and        according to result, it is proceeded further with step a) or the        dosage is ended.

This method enables a stepwise approximation of the desired dosage, thatcan take place completely automatically. An especial skill of theoperator is not necessary.

With advantage the substance intake portion comprises substancecompartments of various size classes and firstly, of the largestpossible size class, the greatest number of substance compartments areemptied in which it is still certain that the desired dosage quantity isnot overshot, then, of the next smaller size class, the greatest numberof substance compartments in which it is still certain that the desireddosage quantity is not overshot are emptied, etc. until the desireddosage quantity with the desired precision is achieved. This enables arapider approximation of the desired dosage quantity.

Preferably the quantity of dosed substance is determined after everyemptying of a substance compartment. After every emptying withsubsequent weight measurement, the situation can then be newlyestimated, due to more exact numbers.

Alternatively, the quantity of dosed substance is determined only afterthe emptying of several substance compartments. Time can be saved inthis manner.

In the case of a preferred embodiment, the substance compartments aretubes, which are filled before step a) by dipping in or insertion insubstance which is found in a supply container, and then afterwardstaken out of the substance again. In such a simple manner and in anautomated way, substance can be taken in by the substance compartments.

With advantage, the weighing balance measures the weight loaded on itbefore and after filling the tubes, and the control means calculatesfrom this, and from the known geometry of the individual tubes, theapproximate quantity of substance in each tube. Then based on thesenumbers, the dosage can immediately begin.

Advantageously after the first, preferably after every, emptying of atube of a size class, the approximate quantity of substance in a tube ofthis size class is newly estimated. This calibration enables a moreprecise determination of the substance quantity in a tube of a certainsize class.

In the case of an advantageous embodiment, after filling of the tubes,firstly at least one tube of each size class is emptied and bygeneration of the weight difference before and after the emptying ofeach tube, the approximate quantity of substance in a tube of this sizeclass is determined. Such a calibration also enables a more precisedetermination of the substance quantity in a tube of a certain sizeclass.

Preferably, dosing firstly takes place in an intermediate container andwhen the desired dosage quantity with the desired precision is achieved,the intermediate container is emptied into the vessel; whereas if thedesired dosage quantity with regard to the desired precision isovershot, the intermediate container is emptied again and the dosage isbegun again. An overdosage can thus also be avoided with very smallweight tolerances.

In the case of an advantageous embodiment, the actual dosage quantity inthe intermediate container is determined by a second weighing balance,on which the intermediate container is fixed. The precision of dosagecan thus be increased.

In the case of an advantageous embodiment with n same substancecompartments, the weight G of the total intaken substance is determinedby weighing, and from the number of the substance compartments n, themass g per substance compartment is calculated:g=G/n  (1)

In the case of an advantageous embodiment, the substance compartmentsare graduated in size classes, the substance compartments within thesame size class having the same volume, so that by the choice of a fewsubstance compartments of various size classes, the entire dosage rangecan be covered. The volumes of the substance compartments of the varioussize classes are in a known ratio to each other. Each of the i sizeclasses comprises n_(i) equally sized substance compartments. In thiscase the calculation of the intaken substance per substance compartmentis carried out according to Formula (2), in which the ratio of thevolume of the individual substance compartment to the total volume isconsidered. The weight of the substance in a substance compartment ofthe size class i is g_(i), the volume ratio is expressed by thecontribution v_(i)/Σ(n_(i)·v_(i)):

$\begin{matrix}{g_{i} = \frac{G \cdot v_{i}}{\sum\limits_{i = 1}^{n}( {n_{i} \cdot v_{i}} )}} & (2)\end{matrix}$

As well it must be pointed out that the expressions “volume” and “volumeratios” always relate to the intaken substance or the substance to beintaken, and not to the empty substance compartments. Notably, thesemeanings apply for the entire patent application. With a cross sectionwhich is uniform in the vertical, the volume ratios of the emptysubstance compartments are the same among each other as those of theintaken substance. In the case of a varying cross section, thecorresponding ratios of the geometric form must be correspondinglycalculated.

The substance compartments filled with substance are brought over thevessel to be filled and the substance compartments are individually(singly or multiplely or all at the same time) or in their entiretyemptied from above by ejection of the intaken substance.

A second aspect of the invention consists in the method for dosage ofsubstances that is possible with the dosing device according to theinvention.

The user firstly establishes a target range about the desired value,within which the achieved value must lie. He also does this in theclassical manual method consciously or unconsciously. The smallestpossible target range corresponds to the mass of the substance to bedosed in a substance compartment of the smallest size class.

If the substance intake portion and the emptying portion are attached ona weighing balance lying above, the total weight of the intakensubstance is thus known from the total weight and the known empty weightof the substance intake portion and the emptying portion. Since thevolume ratios and the number of the substance compartments are alsoknown, the average fill weight per substance compartment for each sizeclass can be calculated according to Formula 2, wherein the individualfill quantities can absolutely have a significant variation. The controlprogram can decide from the average fill weight, which size of substancecompartment should in each case be dosed next, until the target range isreached through ever smaller additions, whereby after each additionweighing takes place, in order to confirm the actual dosed quantity ofsubstance and to decide about the further additions.

EXAMPLE

Substance intake portion and emptying portion 15.0000 g empty: Substanceintake portion and emptying portion after 15.0064 g substance intake:Total intaken weight G: 6.4 mg To dose (desired value and target range):3.32 mg ± 0.01 mg Calculation of the fill quantity per substancecompartment: 1 size class with 10 substance compartments, v₁ = 0.1 μlvolume of these substance compartments: 3 size classes each with 4substance compartments, v₂ = 1 μl, volumes of the substance compartmentsof v₃ = 3 μl, these size classes v₄ = 9 μl,

For the various size classes the following average fill quantities to beexpected are calculated according to Formula 2:g ₁ =G·v ₁/Σ(n _(i) ·v _(i))=6.4 mg·0.1 μl/[(10·0.1 μl)+(4·1 μl)+(4·3μl)+(4·9 μl)]=0.0121 mgg ₂ =G·v ₂/Σ(n _(i) ·v _(i))=6.4 mg·1 μl/[(10·0.1 μl)+(4·1 μl)+(4·3μl)+(4·9 μl)]=0.121 mgg ₃ =G·v ₃/Σ(n _(i) ·v _(i))=6.4 mg·3 μl/[(10·0.1 μl)+(4·1 μl)+(4·3μl)+(4·9 μl)]=0.362 mgg ₄ =G·v ₄/Σ(n _(i) ·v _(i))=6.4 mg·9 μl/[(10·0.1 μl)+(4·1 μl)+(4·3μl)+(4·9 μl)]=1.09 mg

It is then dosed according to the following Table:

Measurement Calculated of the Actual next accumulated last Decisionaddition additions in addition about next Addition in mg mg in mgaction: 0 0 0 0 Addition large 1 1.09 1.003 1.003 Addition large 2 1.092.385 1.382 Addition medium 3 0.362 2.679 0.294 Addition medium 4 0.3623.152 0.473 Addition small 5 0.121 3.281 0.129 Addition finest 6 0.01213.291 0.0099 Addition finest 7 0.0121 3.304 0.0133 Addition finest 80.0121 3.317 0.0125 End

The actual last addition is in each case either calculated on the basisof the previous addition or measured with a second weighing balance.

It is advantageous to always continue to work with the measuredaccumulated value, not with the calculated sum of the individualadditions, so that unavoidable weighing mistakes are not accumulated.

Alternatively to this (for example if only a lower weighing balance isused and thus the total intaken weight is not known, or in order to savetime) the average expelled substance quantity per size class can bedetermined at the beginning of the dosing process by the emptying ofseveral substance compartments with weighing following in each case,i.e. a calibration is undertaken. This can take place directly in thevessel to be filled. With very small substance quantities to be dosedthis step can take place in a waste vessel. Since through this theaverage substance quantity added per size class is known, afterwards byemptying several substance compartments of suitable size at the sametime, dosage can be performed very quickly until a threshold valueunderneath the lower limit of the target range, i.e. a rough dosage iscarried out. In the subsequent fine dosage the control program decidesin turn which size of substance compartment is dosed in each case, untilthe target range is reached, whereby after each addition weighing isperformed.

In the case of an advantageous embodiment, at a suitable time pointduring the dosage process, the actual average fill quantity and thestatistical distribution of the substance quantity per size class iscalculated from the previous addition and/or from the data of thecalibration. The control program can then fit with this distribution thedecision, of which size class is dosed next, with respect to thethreshold value, until which such value the multiple substancecompartments are emptied at the same time. Thus also with veryunfavourable, i.e. wide distribution of the fill quantities, the targetrange is reliably achieved and an overdosing is avoided with asignificantly higher probability.

BRIEF DESCRIPTION OF THE DRAWINGS

In the following, embodiments of the device according to the inventionand the method according to the invention for dosage of substances aredescribed in more detail with reference to the accompanying figures, inwhich:

FIG. 1—shows a perspective view of a substance intake portion and of anemptying portion of a first embodiment of the device according to theinvention for dosage of substances;

FIG. 2—shows a schematic section view of the device from FIG. 1 withsubstance intake portion separated from the emptying portion;

FIG. 3—shows a schematic section view of the substance intake portionand emptying portion which are separated from each other of a secondembodiment of the device according to the invention;

FIG. 4—shows schematically the intake of powdery substance by thesubstance intake portion of FIG. 1 by insertion into substance presentin a supply container;

FIG. 5—shows schematically the intake of fluid substance by thesubstance intake portion from FIG. 1 by dipping into substance presentin a supply container;

FIG. 6—shows schematically the intake of solid substance by thesubstance intake portion from FIG. 1 by insertion into a solid body;

FIG. 7—shows a section view of the lower end of a substance compartmentin the form of a tube which has a pointed lower section;

FIG. 8—shows a section view of the lower end of a substance compartmentin the form of a tube which has a sharp-edged lower section;

FIG. 9—shows a schematic section view of the substance intake portionfrom FIG. 1 with different pre-filled substance compartments which aresealed by foils;

FIG. 10—shows schematically the emptying of a substance compartment by apneumatic pressure surge;

FIG. 11—shows schematically the emptying of a substance compartment by apressure surge mechanically induced by means of a piston movement;

FIG. 12—shows schematically a part of an emptying portion and of asubstance intake portion with a substance compartment filled withpowdery substance;

FIG. 13—shows schematically the emptying of the substance compartmentfrom FIG. 12 by alteration of its geometry by mechanical pressure;

FIG. 14—shows schematically the intake of a powdery substance byinsertion of a substance compartment in substance present in a supplycontainer;

FIG. 15—shows schematically the application of a tension for thealteration of the geometry of the substance compartment from FIG. 14 forthe improvement of the intake of substance;

FIG. 16—shows schematically the emptying of the substance compartmentfrom FIG. 15 by a change of the applied tension for the reversal of thegeometrical alteration;

FIG. 17—shows schematically a part of an emptying portion and of asubstance intake portion with a substance compartment filled with fluidsubstance;

FIG. 18—shows schematically the emptying of the substance compartmentfrom FIG. 17 by alteration of the surface properties of the innersurface of the substance compartment by application of a voltage;

FIG. 19—shows schematically the first embodiment of the device accordingto the invention with a weighing balance, on which the emptying portionand the substance intake portion are fixed, arranged above a vessel tobe filled;

FIG. 20—shows schematically a third embodiment of the device accordingto the invention with a weighing balance arranged below a vessel to befilled;

FIG. 21—shows schematically a fourth embodiment of the device accordingto the invention with a first weighing balance, on which the emptyingportion and the substance intake portion are fixed, arranged above avessel to be filled and a second weighing balance arranged below thevessel to be filled;

FIG. 22—shows a flow diagram of an embodiment of the method according tothe invention for dosage of substances; and

FIG. 23—shows a presentation of an example of the dosage of a substancewith the method presented in FIG. 22.

DETAILED DESCRIPTION

The part of a first embodiment presented in FIGS. 1 and 2 of the deviceaccording to the invention for dosage of substances comprises asubstance intake portion 1 with a carrier plate 12, for example made outof plastic, on which a plurality of substance compartments in the formof tubes 11 are attached, which for example are made out of glass,plastic or metal. Of the tubes 11 which are open above and below, sixtubes are present in each of six size classes. The tubes 11 of a sizeclass have the same inner diameter and are arranged next to each otherin the x-direction. In the y-direction the inner diameters of the tubes11 decrease in terms of size class. Due to the varying inner diameters,the tubes 11 of different size classes normally take in differentquantities of substances to be dosed.

The substance intake portion 1 is detachably fixed via the carrier plate12 to an emptying portion 2. The emptying portion 2 has an emptyingmechanism with which the tubes 11 can be individually emptied. In FIG. 2pistons 122 which are movable in the vertical direction are observable.The pistons 122 are pushed into the tubes 11 and thereby the substancein the tubes 11 concerned is pressed out. Each tube 11 is associatedwith a piston 122. Each piston 122 is individually activatable, whereincustomary driving systems can be used.

The substance intake portion 1 and the emptying portion 2 are preferablyarranged on a displaceable robotic arm, which is not shown. Likewise notshown here is the weighing balance belonging to the device, which isfurther detailed below.

The following applies to the rest of this description. If, in order toclarify the drawings, a figure contains designations which are notexplained in the directly associated text of the description, or viceversa, then you are referred to the point at which they have beenmentioned in previous descriptions of the figures.

FIG. 3 shows the substance intake portion 15 and the emptying portion 2of a second embodiment of the device according to the invention, whereinthe emptying portion 2 with the pistons 122 corresponds to that of thefirst embodiment. However, the substance intake portion 15 comprises asubstance plate 125, for example made out of plastic or metal, intowhich substance compartments 115 are bored. In the lower section in themiddle the substance plate 125 is pointed, which enables a simplerdipping in or insertion into the substance to be dosed. In addition itis lighter and cheaper to produce than the substance intake portion 1according to the first embodiment.

FIG. 4 shows the intake of powdery substance by the tubes 11 of thesubstance intake portion 1 by insertion in substance 5, which is presentin a supply container 4. The vertical arrow indicates the verticaldisplacement of the substance intake portion 1 which is connected withthe emptying portion 2, for insertion of the tubes 11 in the substance5. After the insertion the tubes 11 are taken out of the substance 5again, wherein then due to frictional forces, different quantities ofsubstance 5 remain adhered in the tubes 11, according to the innerdiameter of the tubes 11.

FIG. 5 shows the intake of fluid substance by the tubes 11 of thesubstance intake portion 1 by dipping in fluid substance 50, which ispresent in the supply container 4. The vertical arrow indicates thevertical displacement of the substance intake portion 1 which isconnected with the emptying portion 2, for the dipping in of the tubes11 in the substance 50. After the dipping in, the tubes 11 are taken outof the substance 50 again, wherein then due to capillary forces,different quantities of substance 50 remain adhered in the tubes 11,according to the inner diameter of the tubes 11.

FIG. 6 shows the intake of solid substance by the tubes 11 of thesubstance intake portion 1 by insertion in a solid body 500. The solidbody 500 can be made out of almost any material that permits aninsertion of the tubes 11, for example from polymer material, a wax discor an apple. The vertical arrow indicates the vertical displacement ofthe substance intake portion 1 which is connected with the emptyingportion 2, for insertion of the tubes 11 in the solid body 500. Afterthe insertion the tubes 11 are taken out of the solid body 500 again,wherein then due to frictional forces, different quantities of solidsubstance 500 remain adhered in the tubes 11, according to the innerdiameter of the tubes 11.

In FIG. 7 the lower end of a substance compartment is presented in theform of a tube 110 which has a lower pointed section, while FIG. 8 showsthe lower end of a substance compartment in the form of a tube 111 whichhas a lower sharp-edged section. These special designs of the lower endsof the tubes 110, 111 enable a simpler insertion in powdery or solidsubstances. With fluid substances these special ends lead to a moreregular release of drops, i.e. to uniform actual dosage quantities oftubes 110, 111 of the same size class.

The substance intake portion presented in FIG. 9 corresponds essentiallyto that of FIG. 1, however the tubes 11 are already pre-filled withvarying quantities of substance 5 in regards to size classes. The tubes11 are sealed above and below by foils 14 or 13, such that the substanceintake portion can be transported and stored without problem, so thatsubstance 5 is not lost or contaminated. The foils 13, 14 can beentirely peeled off immediately before use, or alternatively they can bedestroyed when emptying the substance compartments 11, whereinpreferably such foils 13, 14 are used that can be ripped so that noremains of the foil fall in the vessels to be filled.

In the case of the embodiment presented in FIG. 10 the emptying of atube 11 takes place by a pneumatic pressure surge. For this nitrogenunder pressure is let into the tube 11 via a gas line 22, which leads toa pressure surge, which expels out below the tubes 11 the intakensubstance 5. The nitrogen comes for example out of a nitrogen container(not shown) and its admission into the tubes 11 is started by opening avalve 23 arranged in the gas line 22.

In the case of the embodiment presented in FIG. 11 the emptying of atube 11 takes place by a mechanically induced pressure surge. Theemptying portion 102 has for this a cylinder plate 121, which isprovided with a plurality of vertically cylindrical bores, into which apiston 122 is vertically displaceable in each case. A piston 122 ispresent per tube 11, wherein the pistons 122 are individually movableindependently from each other, by means of customary drives.

In the case of the embodiment presented in FIGS. 12 and 13, a tube 211of a substance intake portion 201 is filled with powdery substance 5.The tube 211 has flexible walls, the geometry of which can be changed byexertion of a mechanical pressure. For the exertion of a mechanicalpressure on the tube 211, the emptying portion 202, on which thesubstance intake portion 201 is fixed via a carrier plate 212, haspressure elements 222 in bores in a base plate 221, for example piezoelements, in particular piezo ceramic composite elements. In the presentcase, the tube 211 is enlarged below by exertion of a mechanicalpressure on its upper part, which leads to a release of the intakensubstance 5, and thus to the emptying of the tube 211.

The FIGS. 14 and 15 show the intake of a powdery substance 5 byinsertion of a tube 330 of a substance intake portion in the substance 5present in the supply container 4. After the insertion in the substance5, the lower part of the tube 330, that has at least in its lower partflexible walls, is narrowed by application of a voltage in its upperpart, whereby the substance 5 present in the tube 330 is compacted andwedged in. The application of the voltage takes place by means of anemptying portion, on which the substance intake portion is fixed via acarrier plate 312. The emptying portion has for this voltage electrodes331 and 332, which are positioned in a base plate 321 in such a way thatthey are able to be brought into contact with the tube 330. So that thegeometry of the lower part of the tube 330 changes due to theapplication of a voltage in the upper part, on the lower part, forexample, piezo elements, in particular piezo ceramic composite elements,are attached, which are in electrical conducting connection with theregions of the tube 330 on which the voltage is applied.

After the tube 330 is taken out from the supply container 4 it can befed from above into a vessel 6, into which the substance is to be dosed,for example by means of a robotic arm, on which the emptying portion andthe substance intake portion can be attached. As presented in FIG. 16,the polarity of the applied voltage is then reversed, which withsuitable design of the tube 330 and the piezo elements, leads to anexpansion of the lower part of the tube 330 and to an emptying of thetube 330.

In the case of the embodiment presented in FIGS. 17 and 18 the emptyingportion 302 likewise has voltage electrodes 331 and 332, which arepositioned in a base plate 321 in such a way that they are able to bebrought into contact with a tube 311 containing fluid substance 50. Theemptying portion 302 can, however, additionally or alternatively, alsohave tempering means 322, for example an electrical resistance heating,with which the temperature of the tube 311 can be changed. Also here thesubstance intake portion 301 containing the tube 311 is connected viathe carrier plate 312 with the emptying portion 302.

Through application of a voltage with the voltage electrodes 331 and 332and/or through alteration of the temperature of the tube 311, thesurface properties of the inner surface of the tube 311 can be changedand in this way an emptying of the tube 311 can be initiated. So thatthe surface properties are changed in the desired sense, the innersurface of the tube 311 can be layered for example with asemi-conductor, which by the application of a voltage goes from aninsulated condition into a conducting condition. Thereby the wettabilityof the inner surface of the tube 311 changes, which can initiate theemptying.

FIG. 19 shows schematically the first embodiment of the device accordingto the invention with a weighing balance 3, on which the emptyingportion 2 and the substance intake portion 1 are attached via couplingelements 7, 8, arranged above a vessel 6 to be filled. The weighingbalance 3 is built for example as described in WO 02/29369, which isexplicitly referred to here, and the substance intake portion 1,emptying portion 2 and coupling elements 7, 8 can also be fixed in anequivalent manner.

FIG. 20 shows schematically a third embodiment of the device accordingto the invention with a weighing balance 503 which is arrangedunderneath the vessel 6 to be filled, that can be a conventionalweighing balance.

In the case of the fourth embodiment of the device according to theinvention, which is presented in FIG. 21, the first weighing balance 3,on which the emptying portion 2 and the substance intake portion 1 areattached via the coupling elements 7, 8, is arranged above the vessel 6to be filled; while the second weighing balance 503 is arranged belowthe vessel 6 to be filled. Thus, the quantity of substance expelled fromthe substance intake portion 1, as well as also the quantity ofsubstance accumulated in the vessel 6 can be measured.

FIG. 22 shows a flow diagram of an embodiment of the method according tothe invention for dosage of substances. Firstly the desired value to bereached and, subject to the substance compartments available, the targetrange arising from the desired precision, are established (not shown inthe flow diagram).

Afterwards a calibration K of the substance compartments of the, in thiscase, m different size classes takes place. For this purpose n substancecompartments of a size class are emptied in succession, and after eachemptying weighing will take place. From this the average substancequantity in a substance compartment of this size class can becalculated. All m size classes are calibrated in succession.

After the calibration K, a rough dosage G takes place. Firstly athreshold value, until which a rough dosage can take place without greatdanger of an overdosage, is calculated. After the calculation of thethreshold value, the calculation of the additions of substance stillrequired to reach the threshold value is performed. The calculatedsubstance additions are then undertaken by emptying the correspondingnumber of substance compartments in the vessel to be filled.

In the following fine dosage F, the amount that was dosed in the vesselto be filled is firstly weighed. The measurement result is then comparedwith the target range. If the measurement result lies in the targetrange, the dosage is ended. If it lies underneath the target range, afurther suitable substance compartment is emptied and further weighedetc. until the target range is finally reached.

In FIG. 23 an example of the dosage of a substance with theabove-described method is presented. Firstly the desired value 910 andthe target range 920 are established. Afterwards the m=3 various sizeclasses of substance compartments are calibrated in succession, whereinfor each size class, n=3 emptyings and weighings are performed. Thenfrom this, for each size class, the average substance quantity in asubstance compartment is calculated.

In the subsequent rough dosage G, the threshold value 900, until which arough dosage can take place without great danger of an overdosage, isfirstly calculated. After the calculation of the threshold value, thecalculation of the additions of substance still required to reach thethreshold value is performed and these are subsequently undertaken byemptying the corresponding number of substance compartments in thevessel to be filled.

Finally the fine dosage F takes place, in which the amount that wasdosed in the vessel to be filled is firstly weighed. In the present caseit was shown that the target range 920 was not yet reached and asubstance compartment of the second size class was emptied, once againweighed, again compared with the target range 920, yet another substancecompartment of the third size class was emptied, once again weighed,again compared with the target range 920, once again a substancecompartment of the third size class was emptied, once again weighed andagain compared with the target range 920. It could then be establishedthat the measurement result lay in the target range, and the dosagecould be ended.

Specific embodiments of a device for dosage of subtances according tothe present invention have been described for the purpose ofillustrating the manner in which the invention may be made and used. Itshould be understood that implementation of other variations andmodifications of the invention and its various aspects will be apparentto those skilled in the art, and that the invention is not limited bythe specific embodiments described. It is therefore contemplated tocover by the present invention any and all modifications, variations, orequivalents that fall within the true spirit and scope of the basicunderlying principles disclosed and claimed herein.

1. A device for dosage of substances comprising: a substance intakeportion, having a plurality of substance compartments for the intake ofthe substance to be dosed; an emptying portion for the complete emptyingof at least one of the substance compartments each time in one step; aweighing balance for the determination of the quantity of dosedsubstance; and a control means for controlling the complete emptying ofany one or more of the substance compartments each time in one step asneeded dependent on the quantity of dosed substance as determined bymeans of the weighing balance.
 2. The device according to claim 1,wherein the substance intake portion comprises substance compartments ofvarious size classes, with which various quantities of substance to bedosed can be obtained.
 3. The device according to claim 2, wherein atleast some of the size classes are graduated across at least a factor of5, preferably in the ratio 1:2:5.
 4. The device according claim 1,wherein at least some of the substance compartments are pre-filled withthe substance to be dosed and preferably are sealed.
 5. The deviceaccording to claim 1, wherein the substance compartments are formed asvertically arranged tubes.
 6. The device according to claim 5, whereinthe tubes of different size classes have different inner diameters. 7.The device according to claim 5 wherein the inner diameters of the tubesare smaller than 5 mm, preferably smaller than 1 mm, more preferablysmaller than 0.5 mm, in particular preferably smaller than 0.1 mm. 8.The device according to claim 5, wherein at least some of the tubesnarrow progressively from the top of the tube to the bottom of the tube.9. The device according to claim 5, wherein at least some of the tubeshave pointed or sharp-edged lower sections.
 10. The device according toclaim 5, wherein at least some of the tubes are pre-filled with thesubstance to be dosed and preferably the two ends of the tubes aresealed with foil.
 11. The device according to claim 1 wherein at leastsome of the substance compartments have an inner surface with anarithmetic mean roughness value R_(a) larger than 0.5 μm.
 12. The deviceaccording to claim 1, further comprising various classes of substancecompartments with inner surfaces with different arithmetic meanroughness values R_(a).
 13. The device according to claim 1, wherein atleast some of the substance compartments have, on their inner surface,flexible lamellae and/or barbs.
 14. The device according to claim 1,further comprising various classes of substance compartments with innersurfaces with different wettability.
 15. The device according to claim1, wherein the substance intake portion is automatically removable fromthe emptying portion.
 16. The device according to claim 1, wherein thesubstance compartments are individually mounted in the substance intakeportion and their number is variable.
 17. The device according to claim1, wherein the substance compartments in the substance intake portionare individually displaceably mounted between a fill position, in whichthey are fillable, and an inactive position, in which they are notfillable.
 18. The device according to claim 1, further comprising meansfor vertical displacement of the substance intake portion.
 19. Thedevice according to claim 1, wherein the emptying portion comprisesmeans for the admission of pressure gas into every individual substancecompartments.
 20. The device according to claim 1, wherein for everysubstance compartment the emptying portion has a displaceable piston.21. The device according to claim 1 wherein the emptying portion hasmeans for the alteration of the geometry of every individual substancecompartment, which further comprise means for the production of amechanical pressure, a voltage or a temperature change.
 22. The deviceaccording to claim 1, wherein the emptying portion has means for thealteration of the surface properties of the inner surface of everyindividual substance compartment, which further comprise means for theproduction of a voltage and/or a temperature change.
 23. The deviceaccording to claim 1 wherein the emptying portion has means for thealteration of the flow properties of the substance to be dosed in everyindividual substance compartment, which further comprise means for theproduction of a voltage or a temperature change.
 24. The deviceaccording to claim 1, wherein the emptying portion and the substanceintake portion are arranged on the weighing balance such that they areweighed by said weighing balance.
 25. The device according to claim 1,wherein the weighing balance or a second weighing balance is designed inorder to receive a vessel to be filled and to measure the weight of thevessel and the substance dosed into the vessel.
 26. A method for dosageof substances with a device for dosage of substances having a substanceintake portion, with a plurality of substance compartments for theintake of the substance to be dosed; an emptying portion for thecomplete emptying of at least one of the substance compartments eachtime in one step; a weighing balance for the determination of thequantity of dosed substance; and, a control means for controlling thecomplete emptying of any one or more of the substance compartments eachtime in one step as needed dependent on the quantity of dosed substanceas determined by means of the weighing balance; the method comprising:a) completely emptying in one step at least one substance compartment ofa substance intake portion containing a substance such that substance isdosed into a vessel; b) determining the quantity of substance dosed inthe vessel using a weighing balance; and c) calculating with the controlmeans whether, and if need be, how much additional substance must bedosed into the vessel, and according to the calculation result, eitherrepeating steps a) to c) or stopping.
 27. The method according to claim26, wherein the substance intake portion comprises substancecompartments of varying size classes, and starting with the greatestpossible number of substance compartments of the largest possible sizeclass being emptied into the vessel while it is still certain that thedesired dosage quantity is not exceeded, then, proceeding with thegreatest possible number of substance compartments of the next smallersize class being emptied into the vessel while it is still certain thatthe desired dosage quantity is not exceeded, and repeating until thedesired dosage quantity with the desired precision is achieved.
 28. Themethod according to claim 26, wherein the quantity of dosed substance isdetermined after every emptying of a substance compartment.
 29. Themethod according to claim 26, wherein the quantity of dosed substance isdetermined only after the emptying of several substance compartments.30. The method according to claim 26, wherein the substance compartmentsare filled before step a) by dipping them in or inserting them insubstance which is found in a supply container, and then removing thecompartments from the container.
 31. The method according to claim 30,wherein the weighing balance measures the weight loaded on it before andafter filling of the substance compartments, and the control meanscalculates from this, and from the known geometry of the individualsubstance compartments, the approximate quantity of substance in eachsubstance compartment.
 32. The method according to claim 30, whereinafter every emptying of a substance compartment of a size class, theapproximate quantity of substance in the remaining substancecompartments of this size class is newly estimated.
 33. The methodaccording to claim 30, wherein after the filling of the substancecompartments, at least one substance compartment of each size class isemptied and by calculation of the weight difference before and after theemptying of each substance compartment, the approximate quantity ofsubstance in a substance compartment of this size class is determined.34. The method according to claim 26, wherein dosing first takes placein an intermediate container, and when the desired dosage quantity withthe desired precision is achieved, the intermediate container is emptiedinto the vessel; whereas if the desired dosage quantity with regard tothe desired precision is exceeded, the intermediate container is emptiedagain and the dosage is begun again.
 35. The method according to claim34, wherein the actual dosage quantity in the intermediate container isdetermined by a second weighing balance on which the intermediatecontainer is arranged for measurement.